Receptor-activated G proteins are heterotrimeric, consisting of α, β, and γ subunits. The β and γ subunits form a tight complex, but when the G protein is activated the α subunit affinity for the β/γ complex is reduced. The result is that two signaling elements arise from the G protein activation and can act on different intracellular targets. The GPCRs act predominantly on three G protein subclasses: Gi/o, Gq-like, and Gs-like (Wickman and Clapham 1995). The Gi/o G protein class has net inhibitory effects on neuronal function, through actions of both the α and β/γ protein subunits. For example, the α subunit inhibits the enzyme adenylyl cylase (AC) that normally generates the second messenger cAMP. The β/γ subunits activate potassium channels that inhibit neuronal activity (the so-called G protein-activated inward rectifier, GIRK, potassium channels). The β/γ subunits also inhibit the function of voltage-gated calcium channels, leading to inhibition of neurotransmitter release, and also appear to have more direct effects on vesicle fusion (Dolphin 2003; Elmslie 2003; Miller 1998; Wu and Saggau 1994). The Gq-like α subunits activate protein and lipid
